EFFECT OF GLIBENCLAMIDE ON EXTRACELLULAR POTASSIUM ACCUMULATION AND THE ELECTROPHYSIOLOGICAL CHANGES DURING MYOCARDIAL-ISCHEMIA IN THE ARTERIALLY PERFUSED INTERVENTRICULAR SEPTUM OF RABBIT

Study objective - The aim was to study the effects of glibenclamide on the rate of rise of extracellular potassium concentration ([K+]o) and the electrophysiological changes that occur during myocardial ischaemia. Design - The study was performed in isolated, arterially perfused interventricular septa from the rabbit. Six septa were treated with glibenclamide 10(-6) mol.litre-1 and there were six untreated controls (vehicle only). [K+]o and electrophysiological variables were compared before and during a 30 min period of global zero flow ischaemia. Measurements and main results - Prior to ischaemia, the extracellular potassium concentrations measured using potassium sensitive valinomycin electrodes were similar in the control and glibenclamide groups being 4.0 (SEM 0.1) and 4.0 (0.1) mmol.litre-1 respectively. [K+]o rose during ischaemia in both groups, and at 30 min was 13.3 (0.7) mmol.litre-1 in the control group. The increase in the glibenclamide group was less marked, reaching 9.2 (0.5) mmol.litre-1 (p < 0.0005; unpaired t test). Glibenclamide had no electrophysiological effects prior to ischaemia. However, during ischaemia the decrease in action potential amplitude, action potential duration (APD), maximum upstroke velocity of the action potentials (dV/dt(max)), and the extent of resting membrane potential (Em) depolarisation were less in the glibenclamide group than in the controls. The effective refractory period (ERP) progressively shortened over the 30 min of ischaemia in both groups, to a similar extent. When taken in conjunction with the relative changes in action potential duration the degree of post-repolarisation refractoriness (ERP-APD) that developed was less in the glibenclamide group than in the controls. Conclusions - Glibenclamide attenuated the ischaemic rise in [K+]o, with preservation of both membrane potential and action potential amplitude, duration, and upstroke velocity together with less post-repolarisation refractoriness. These effects could be potentially antiarrhythmic in acute myocardial ischaemia.